Dual Inhibition of IGF-1R and ErbB3 Enhances the Activity of Gemcitabine and Nab-Paclitaxel in Preclinical Models of Pancreatic Cancer

Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinica...

Full description

Saved in:
Bibliographic Details
Published inClinical cancer research Vol. 24; no. 12; pp. 2873 - 2885
Main Authors Camblin, Adam J, Pace, Emily A, Adams, Sharlene, Curley, Michael D, Rimkunas, Victoria, Nie, Lin, Tan, Gege, Bloom, Troy, Iadevaia, Sergio, Baum, Jason, Minx, Charlene, Czibere, Akos, Louis, Chrystal U, Drummond, Daryl C, Nielsen, Ulrik B, Schoeberl, Birgit, Pipas, J Marc, Straubinger, Robert M, Askoxylakis, Vasileios, Lugovskoy, Alexey A
Format Journal Article
LanguageEnglish
Published United States American Association for Cancer Research Inc 15.06.2018
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies. Growth factor screening in pancreatic cancer cell lines was performed to identify activators of prosurvival PI3K/AKT signaling. The prevalence of activating growth factors and their receptors was assessed in pancreatic cancer patient samples. Effects of a bispecific IGF-1R and ErbB3 targeting antibody on receptor expression, signaling, cancer cell viability and apoptosis, spheroid growth, and chemotherapy activity in pancreatic cancer xenograft models were determined. Growth factor screening in pancreatic cancer cells revealed insulin-like growth factor 1 (IGF-1) and heregulin (HRG) as the most potent AKT activators. Both growth factors reduced pancreatic cancer cell sensitivity to gemcitabine or paclitaxel in spheroid growth assays. Istiratumab (MM-141), a novel bispecific antibody that blocks IGF-1R and ErbB3, restored the activity of paclitaxel and gemcitabine in the presence of IGF-1 and HRG Dual IGF-1R/ErbB3 blocking enhanced chemosensitivity through inhibition of AKT phosphorylation and promotion of IGF-1R and ErbB3 degradation. Addition of istiratumab to gemcitabine and nab-paclitaxel improved chemotherapy activity Our findings suggest a critical role for the HRG/ErbB3 axis and support the clinical exploration of dual IGF-1R/ErbB3 blocking in pancreatic cancer. .
AbstractList Purpose: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies. Experimental Design: Growth factor screening in pancreatic cancer cell lines was performed to identify activators of prosurvival PI3K/AKT signaling. The prevalence of activating growth factors and their receptors was assessed in pancreatic cancer patient samples. Effects of a bispecific IGF-1R and ErbB3 targeting antibody on receptor expression, signaling, cancer cell viability and apoptosis, spheroid growth, and in vivo chemotherapy activity in pancreatic cancer xenograft models were determined. Results: Growth factor screening in pancreatic cancer cells revealed insulin-like growth factor 1 (IGF-1) and heregulin (HRG) as the most potent AKT activators. Both growth factors reduced pancreatic cancer cell sensitivity to gemcitabine or paclitaxel in spheroid growth assays. Istiratumab (MM-141), a novel bispecific antibody that blocks IGF-1R and ErbB3, restored the activity of paclitaxel and gemcitabine in the presence of IGF-1 and HRG in vitro. Dual IGF-1R/ErbB3 blocking enhanced chemosensitivity through inhibition of AKT phosphorylation and promotion of IGF-1R and ErbB3 degradation. Addition of istiratumab to gemcitabine and nab-paclitaxel improved chemotherapy activity in vivo. Conclusions: Our findings suggest a critical role for the HRG/ErbB3 axis and support the clinical exploration of dual IGF-1R/ErbB3 blocking in pancreatic cancer. Clin Cancer Res; 24(12); 2873–85. ©2018 AACR.
Purpose: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies.Experimental Design: Growth factor screening in pancreatic cancer cell lines was performed to identify activators of prosurvival PI3K/AKT signaling. The prevalence of activating growth factors and their receptors was assessed in pancreatic cancer patient samples. Effects of a bispecific IGF-1R and ErbB3 targeting antibody on receptor expression, signaling, cancer cell viability and apoptosis, spheroid growth, and in vivo chemotherapy activity in pancreatic cancer xenograft models were determined.Results: Growth factor screening in pancreatic cancer cells revealed insulin-like growth factor 1 (IGF-1) and heregulin (HRG) as the most potent AKT activators. Both growth factors reduced pancreatic cancer cell sensitivity to gemcitabine or paclitaxel in spheroid growth assays. Istiratumab (MM-141), a novel bispecific antibody that blocks IGF-1R and ErbB3, restored the activity of paclitaxel and gemcitabine in the presence of IGF-1 and HRG in vitro. Dual IGF-1R/ErbB3 blocking enhanced chemosensitivity through inhibition of AKT phosphorylation and promotion of IGF-1R and ErbB3 degradation. Addition of istiratumab to gemcitabine and nab-paclitaxel improved chemotherapy activity in vivo.Conclusions: Our findings suggest a critical role for the HRG/ErbB3 axis and support the clinical exploration of dual IGF-1R/ErbB3 blocking in pancreatic cancer. Clin Cancer Res; 24(12); 2873–85. ©2018 AACR.
Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies. Growth factor screening in pancreatic cancer cell lines was performed to identify activators of prosurvival PI3K/AKT signaling. The prevalence of activating growth factors and their receptors was assessed in pancreatic cancer patient samples. Effects of a bispecific IGF-1R and ErbB3 targeting antibody on receptor expression, signaling, cancer cell viability and apoptosis, spheroid growth, and chemotherapy activity in pancreatic cancer xenograft models were determined. Growth factor screening in pancreatic cancer cells revealed insulin-like growth factor 1 (IGF-1) and heregulin (HRG) as the most potent AKT activators. Both growth factors reduced pancreatic cancer cell sensitivity to gemcitabine or paclitaxel in spheroid growth assays. Istiratumab (MM-141), a novel bispecific antibody that blocks IGF-1R and ErbB3, restored the activity of paclitaxel and gemcitabine in the presence of IGF-1 and HRG Dual IGF-1R/ErbB3 blocking enhanced chemosensitivity through inhibition of AKT phosphorylation and promotion of IGF-1R and ErbB3 degradation. Addition of istiratumab to gemcitabine and nab-paclitaxel improved chemotherapy activity Our findings suggest a critical role for the HRG/ErbB3 axis and support the clinical exploration of dual IGF-1R/ErbB3 blocking in pancreatic cancer. .
Author Rimkunas, Victoria
Schoeberl, Birgit
Straubinger, Robert M
Nie, Lin
Baum, Jason
Louis, Chrystal U
Pipas, J Marc
Lugovskoy, Alexey A
Camblin, Adam J
Curley, Michael D
Iadevaia, Sergio
Pace, Emily A
Bloom, Troy
Adams, Sharlene
Czibere, Akos
Nielsen, Ulrik B
Askoxylakis, Vasileios
Tan, Gege
Drummond, Daryl C
Minx, Charlene
Author_xml – sequence: 1
  givenname: Adam J
  surname: Camblin
  fullname: Camblin, Adam J
  email: acamblin@merrimack.com, VAskoxylakis@merrimack.com
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts. acamblin@merrimack.com VAskoxylakis@merrimack.com
– sequence: 2
  givenname: Emily A
  surname: Pace
  fullname: Pace, Emily A
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 3
  givenname: Sharlene
  surname: Adams
  fullname: Adams, Sharlene
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 4
  givenname: Michael D
  surname: Curley
  fullname: Curley, Michael D
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 5
  givenname: Victoria
  surname: Rimkunas
  fullname: Rimkunas, Victoria
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 6
  givenname: Lin
  surname: Nie
  fullname: Nie, Lin
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 7
  givenname: Gege
  surname: Tan
  fullname: Tan, Gege
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 8
  givenname: Troy
  surname: Bloom
  fullname: Bloom, Troy
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 9
  givenname: Sergio
  surname: Iadevaia
  fullname: Iadevaia, Sergio
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 10
  givenname: Jason
  surname: Baum
  fullname: Baum, Jason
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 11
  givenname: Charlene
  surname: Minx
  fullname: Minx, Charlene
  organization: Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York
– sequence: 12
  givenname: Akos
  surname: Czibere
  fullname: Czibere, Akos
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 13
  givenname: Chrystal U
  surname: Louis
  fullname: Louis, Chrystal U
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 14
  givenname: Daryl C
  surname: Drummond
  fullname: Drummond, Daryl C
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 15
  givenname: Ulrik B
  surname: Nielsen
  fullname: Nielsen, Ulrik B
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 16
  givenname: Birgit
  surname: Schoeberl
  fullname: Schoeberl, Birgit
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 17
  givenname: J Marc
  surname: Pipas
  fullname: Pipas, J Marc
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
– sequence: 18
  givenname: Robert M
  orcidid: 0000-0003-0870-9236
  surname: Straubinger
  fullname: Straubinger, Robert M
  organization: Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York
– sequence: 19
  givenname: Vasileios
  surname: Askoxylakis
  fullname: Askoxylakis, Vasileios
  email: acamblin@merrimack.com, VAskoxylakis@merrimack.com
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts. acamblin@merrimack.com VAskoxylakis@merrimack.com
– sequence: 20
  givenname: Alexey A
  surname: Lugovskoy
  fullname: Lugovskoy, Alexey A
  organization: Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29549161$$D View this record in MEDLINE/PubMed
BookMark eNpdkctu1DAYRi1URC_wCCBLbLpx8W_HlyxLmA4jtWVUwdpyHEfjKuMUO0HtC_DcOPSy6MoXne_z5RyjgzhGj9BHoGcAQn8BqjShFWdnTXNDQBHGJHuDjkAIRTiT4qDMn5lDdJzzLaVQAa3eoUNWi6oGCUfo77fZDngTd6ENUxgjHnu8WV8QuME2dniV2q8cr-LORucznnYen7sp_AnTw0Ku_d6FybYh-v_4tW3J1rqh7N37AYeIt8mXZQyunHI1dn7IS25b6pK3U3C4WZrTe_S2t0P2H57GE_TrYvWz-U4uf6w3zfklcZXWE6l6XXHZcst6JWvNvHKedn3nuGuhFrwCa2vpeqWBCt8Cp7aiXEnrynOV1PwEnT723qXx9-zzZPYhOz8MNvpxzoaVL6qFrAEK-vkVejvOKZbbFUoIrkUtZaHEI-XSmHPyvblLYW_TgwFqFlFmkWAWCaaIMqDMIqrkPj21z-3edy-pZzP8H_31jlU
CitedBy_id crossref_primary_10_1155_2021_6945046
crossref_primary_10_1016_j_ejmech_2020_112661
crossref_primary_10_3389_fonc_2021_683788
crossref_primary_10_1016_j_lfs_2022_121211
crossref_primary_10_3390_ijms231810382
crossref_primary_10_3390_cancers11081128
crossref_primary_10_3389_fphar_2022_961788
crossref_primary_10_1002_adbi_201900236
crossref_primary_10_1001_jamanetworkopen_2023_24977
crossref_primary_10_1093_neuonc_noac054
crossref_primary_10_1158_1055_9965_EPI_19_1315
crossref_primary_10_1016_j_canlet_2021_08_029
crossref_primary_10_1186_s13046_022_02515_x
crossref_primary_10_12998_wjcc_v10_i27_9703
crossref_primary_10_3892_or_2021_8134
crossref_primary_10_1016_j_annonc_2019_09_004
crossref_primary_10_11569_wcjd_v29_i8_421
crossref_primary_10_3389_fcell_2021_634512
crossref_primary_10_1002_ijc_32273
crossref_primary_10_1080_14728214_2021_1905795
crossref_primary_10_1016_j_gene_2023_148007
crossref_primary_10_1016_j_canlet_2020_10_051
crossref_primary_10_3390_cancers12071849
crossref_primary_10_1021_acs_chemrev_8b00467
crossref_primary_10_3390_cells10081856
crossref_primary_10_20517_cdr_2024_11
crossref_primary_10_1158_2767_9764_CRC_22_0256
crossref_primary_10_1007_s12094_024_03492_7
crossref_primary_10_18632_oncotarget_28421
crossref_primary_10_3390_biomedicines11010119
crossref_primary_10_1038_s41419_022_05103_1
crossref_primary_10_1186_s13045_020_00904_3
crossref_primary_10_1016_j_gendis_2022_03_002
crossref_primary_10_1016_j_pan_2019_08_008
crossref_primary_10_1038_s41598_019_53322_y
crossref_primary_10_1016_j_drup_2022_100864
crossref_primary_10_1016_j_anndiagpath_2021_151883
Cites_doi 10.1097/JTO.0b013e31818180f5
10.1158/1078-0432.CCR-12-1840
10.1073/pnas.1318415110
10.2147/IJN.S88084
10.1158/1078-0432.CCR-13-3396
10.4161/cbt.10.6.12532
10.4161/mabs.23363
10.1126/science.1164368
10.1007/s10620-013-2673-2
10.1038/npjsba.2016.34
10.1158/0008-5472.CAN-09-3321
10.1016/j.ccr.2014.02.025
10.1038/nrc1387
10.1073/pnas.1016140108
10.3109/07357907.2014.905586
10.1038/nature05474
10.1073/pnas.0912101106
10.1126/science.1141478
10.1002/j.1460-2075.1995.tb00101.x
10.1038/bjc.2014.215
10.1093/annonc/mdv027
10.1038/ncomms3516
10.1093/jnci/91.7.620
10.1056/NEJMoa1304369
10.1371/journal.pone.0106249
10.1200/jco.2015.33.3_suppl.295
10.1056/NEJMoa1011923
10.1158/0008-5472.CAN-16-1201
10.4161/cbt.9.10.11534
10.1002/cncr.28744
10.1016/S0140-6736(15)00986-1
10.1016/j.ccr.2012.01.007
10.1016/S0140-6736(97)10384-1
10.1016/j.bbrc.2013.06.030
10.1038/bjc.2011.263
10.1007/BF02254995
10.4161/mabs.3.3.15299
10.1186/bcr3018
10.1146/annurev-bioeng-071813-105259
10.1016/j.bbcan.2006.05.003
10.1126/science.279.5350.563
10.1007/s13277-013-1131-2
10.1016/j.gtc.2011.12.001
10.1021/jm9002395
10.1158/1535-7163.MCT-13-0255
10.1126/scitranslmed.aal4682
10.1126/science.1171362
10.1186/1471-2407-13-392
10.1093/annonc/mds142
ContentType Journal Article
Copyright 2018 American Association for Cancer Research.
Copyright American Association for Cancer Research Inc Jun 15, 2018
Copyright_xml – notice: 2018 American Association for Cancer Research.
– notice: Copyright American Association for Cancer Research Inc Jun 15, 2018
DBID NPM
AAYXX
CITATION
7QO
7T5
7TO
7U9
8FD
FR3
H94
P64
7X8
DOI 10.1158/1078-0432.CCR-17-2262
DatabaseName PubMed
CrossRef
Biotechnology Research Abstracts
Immunology Abstracts
Oncogenes and Growth Factors Abstracts
Virology and AIDS Abstracts
Technology Research Database
Engineering Research Database
AIDS and Cancer Research Abstracts
Biotechnology and BioEngineering Abstracts
MEDLINE - Academic
DatabaseTitle PubMed
CrossRef
Virology and AIDS Abstracts
Biotechnology Research Abstracts
Oncogenes and Growth Factors Abstracts
Technology Research Database
AIDS and Cancer Research Abstracts
Immunology Abstracts
Engineering Research Database
Biotechnology and BioEngineering Abstracts
MEDLINE - Academic
DatabaseTitleList CrossRef
Virology and AIDS Abstracts
PubMed
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1557-3265
EndPage 2885
ExternalDocumentID 10_1158_1078_0432_CCR_17_2262
29549161
Genre Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID ---
18M
29B
2FS
2WC
34G
39C
476
53G
5GY
5RE
5VS
6J9
ABOCM
ACGFO
ACIWK
ACPRK
ACSVP
ADBBV
ADCOW
ADNWM
AENEX
AFHIN
AFOSN
AFRAH
ALMA_UNASSIGNED_HOLDINGS
BAWUL
BR6
BTFSW
CS3
DIK
DU5
E3Z
EBS
EJD
F5P
FRP
GX1
H13
IH2
KQ8
L7B
LSO
NPM
OK1
P0W
P2P
QTD
RCR
RHF
RHI
RNS
SJN
TR2
W2D
W8F
WOQ
YKV
AAYXX
CITATION
7QO
7T5
7TO
7U9
8FD
FR3
H94
P64
7X8
ID FETCH-LOGICAL-c488t-4f8436b3a2f76982e7ce0dfdc3cb195341aa96cf78105eb130a40376ac4917683
ISSN 1078-0432
IngestDate Fri Aug 16 23:20:02 EDT 2024
Thu Oct 10 22:19:05 EDT 2024
Thu Nov 21 22:45:32 EST 2024
Sat Sep 28 08:38:32 EDT 2024
IsDoiOpenAccess false
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 12
Language English
License 2018 American Association for Cancer Research.
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c488t-4f8436b3a2f76982e7ce0dfdc3cb195341aa96cf78105eb130a40376ac4917683
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0003-0870-9236
OpenAccessLink https://doi.org/10.1158/1078-0432.22465550
PMID 29549161
PQID 2055385966
PQPubID 2046235
PageCount 13
ParticipantIDs proquest_miscellaneous_2014956911
proquest_journals_2055385966
crossref_primary_10_1158_1078_0432_CCR_17_2262
pubmed_primary_29549161
PublicationCentury 2000
PublicationDate 2018-06-15
20180615
PublicationDateYYYYMMDD 2018-06-15
PublicationDate_xml – month: 06
  year: 2018
  text: 2018-06-15
  day: 15
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: Philadelphia
PublicationTitle Clinical cancer research
PublicationTitleAlternate Clin Cancer Res
PublicationYear 2018
Publisher American Association for Cancer Research Inc
Publisher_xml – name: American Association for Cancer Research Inc
References Shin (2022061100531905700_bib2) 2012; 41
Wallasch (2022061100531905700_bib33) 1995; 14
Chauhan (2022061100531905700_bib49) 2013; 4
Chan (2022061100531905700_bib10) 1998; 279
Philip (2022061100531905700_bib42) 2014; 120
Kodack (2022061100531905700_bib39) 2017; 9
Li (2022061100531905700_bib8) 2009; 52
Garrett (2022061100531905700_bib35) 2011; 108
Ma (2022061100531905700_bib14) 1999; 91
Knowlden (2022061100531905700_bib23) 2011; 13
Wang-Gillam (2022061100531905700_bib44) 2015; 33s
Eser (2022061100531905700_bib26) 2014; 111
Kawanami (2022061100531905700_bib28) 2012; 27
Fuchs (2022061100531905700_bib20) 2015; 26
Jain (2022061100531905700_bib47) 2014; 16
Griffon-Etienne (2022061100531905700_bib48) 1999; 59
Jia (2022061100531905700_bib24) 2013; 436
Engelman (2022061100531905700_bib36) 2007; 316
Liles (2022061100531905700_bib40) 2010; 10
Cao (2022061100531905700_bib52) 2014; 9
Von Hoff (2022061100531905700_bib3) 2013; 369
Huang (2022061100531905700_bib22) 2010; 70
Dziadziuszko (2022061100531905700_bib15) 2008; 3
Arteaga (2022061100531905700_bib38) 2014; 25
Preis (2022061100531905700_bib27) 2010; 9
Wang-Gillam (2022061100531905700_bib6) 2016; 387
Ko (2022061100531905700_bib5) 2016; 11
Ireland (2022061100531905700_bib30) 2016; 76
McCaffery (2022061100531905700_bib19) 2013; 19
Kurmasheva (2022061100531905700_bib7) 2006; 1766
Hankinson (2022061100531905700_bib12) 1998; 351
Jura (2022061100531905700_bib32) 2009; 106
Conroy (2022061100531905700_bib4) 2011; 364
American Cancer Society (2022061100531905700_bib1) 2015
Zhang (2022061100531905700_bib25) 2014; 20
Jones (2022061100531905700_bib31) 2008; 321
Hirakawa (2022061100531905700_bib17) 2013; 13
Pollak (2022061100531905700_bib9) 2004; 4
Liu (2022061100531905700_bib13) 2002; 9
Sergina N (2022061100531905700_bib37) 2007; 445
Fitzgerald (2022061100531905700_bib21) 2014; 13
Xu (2022061100531905700_bib45) 2013; 5
Adachi (2022061100531905700_bib11) 2014; 35
Tian (2022061100531905700_bib29) 2013; 58
Fitzgerald (2022061100531905700_bib43) 2011; 3
Liles (2022061100531905700_bib41) 2011; 105
Stylianopoulos (2022061100531905700_bib46) 2013; 110
Jiang (2022061100531905700_bib16) 2014; 32
Olive (2022061100531905700_bib50) 2009; 324
Schoeberl (2022061100531905700_bib34) 2017; 3
Provenzano (2022061100531905700_bib51) 2012; 21
Kindler (2022061100531905700_bib18) 2012; 23
References_xml – volume: 3
  start-page: 815
  year: 2008
  ident: 2022061100531905700_bib15
  article-title: The insulin-like growth factor pathway in lung cancer
  publication-title: J Thorac Oncol
  doi: 10.1097/JTO.0b013e31818180f5
  contributor:
    fullname: Dziadziuszko
– volume: 19
  start-page: 4282
  year: 2013
  ident: 2022061100531905700_bib19
  article-title: Putative predictive biomarkers of survival in patients with metastatic pancreatic adenocarcinoma treated with gemcitabine and ganitumab, an IGF1R inhibitor
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-12-1840
  contributor:
    fullname: McCaffery
– volume: 110
  start-page: 18632
  year: 2013
  ident: 2022061100531905700_bib46
  article-title: Combining two strategies to improve perfusion and drug delivery in solid tumors
  publication-title: Proc Natl Acad Sci
  doi: 10.1073/pnas.1318415110
  contributor:
    fullname: Stylianopoulos
– volume: 11
  start-page: 1225
  year: 2016
  ident: 2022061100531905700_bib5
  article-title: Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan
  publication-title: Int J Nanomedicine
  doi: 10.2147/IJN.S88084
  contributor:
    fullname: Ko
– volume: 20
  start-page: 4559
  year: 2014
  ident: 2022061100531905700_bib25
  article-title: Functional genetic approach identifies MET, HER3, IGF1R, INSR pathways as determinants of lapatinib unresponsiveness in HER2-positive gastric cancer
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-13-3396
  contributor:
    fullname: Zhang
– volume: 10
  start-page: 555
  year: 2010
  ident: 2022061100531905700_bib40
  article-title: ErbB3 expression promotes tumorigenesis in pancreatic adenocarcinoma
  publication-title: Cancer Biol Ther
  doi: 10.4161/cbt.10.6.12532
  contributor:
    fullname: Liles
– volume: 5
  start-page: 237
  year: 2013
  ident: 2022061100531905700_bib45
  article-title: Rapid optimization and prototyping for therapeutic antibody-like molecules
  publication-title: MAbs
  doi: 10.4161/mabs.23363
  contributor:
    fullname: Xu
– volume: 321
  start-page: 1801
  year: 2008
  ident: 2022061100531905700_bib31
  article-title: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses
  publication-title: Science
  doi: 10.1126/science.1164368
  contributor:
    fullname: Jones
– volume: 58
  start-page: 2705
  year: 2013
  ident: 2022061100531905700_bib29
  article-title: Insulin-like growth factor 1 receptor promotes the growth and chemoresistance of pancreatic cancer
  publication-title: Dig Dis Sci
  doi: 10.1007/s10620-013-2673-2
  contributor:
    fullname: Tian
– volume: 3
  start-page: 16034
  year: 2017
  ident: 2022061100531905700_bib34
  article-title: Systems biology driving drug development: from design to the clinical testing of the anti-ErbB3 antibody seribantumab (MM-121)
  publication-title: NPJ Syst Biol Appl
  doi: 10.1038/npjsba.2016.34
  contributor:
    fullname: Schoeberl
– volume: 70
  start-page: 1204
  year: 2010
  ident: 2022061100531905700_bib22
  article-title: Heterotrimerization of the growth factor receptors erbB2, erbB3, and insulin-like growth factor-i receptor in breast cancer cells resistant to herceptin
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-09-3321
  contributor:
    fullname: Huang
– volume: 25
  start-page: 282
  year: 2014
  ident: 2022061100531905700_bib38
  article-title: ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2014.02.025
  contributor:
    fullname: Arteaga
– volume: 4
  start-page: 505
  year: 2004
  ident: 2022061100531905700_bib9
  article-title: Insulin-like growth factors and neoplasia
  publication-title: Nat Rev Cancer
  doi: 10.1038/nrc1387
  contributor:
    fullname: Pollak
– volume: 108
  start-page: 5021
  year: 2011
  ident: 2022061100531905700_bib35
  article-title: Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1016140108
  contributor:
    fullname: Garrett
– volume: 32
  start-page: 218
  year: 2014
  ident: 2022061100531905700_bib16
  article-title: Identification of novel predictive markers for the prognosis of pancreatic ductal adenocarcinoma
  publication-title: Cancer Invest
  doi: 10.3109/07357907.2014.905586
  contributor:
    fullname: Jiang
– volume: 445
  start-page: 437
  year: 2007
  ident: 2022061100531905700_bib37
  article-title: Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3
  publication-title: Nature
  doi: 10.1038/nature05474
  contributor:
    fullname: Sergina N
– volume: 27
  start-page: 867
  year: 2012
  ident: 2022061100531905700_bib28
  article-title: A humanized anti-IGF-1R monoclonal antibody (R1507) and/or metformin enhance gemcitabine-induced apoptosis in pancreatic cancer cells
  publication-title: Oncol Rep
  contributor:
    fullname: Kawanami
– volume: 59
  start-page: 3776
  year: 1999
  ident: 2022061100531905700_bib48
  article-title: Taxane-induced apoptosis decompresses blood vessels and lowers interstitial fluid pressure in solid tumors: clinical implications
  publication-title: Cancer Res
  contributor:
    fullname: Griffon-Etienne
– volume: 106
  start-page: 21608
  year: 2009
  ident: 2022061100531905700_bib32
  article-title: Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.0912101106
  contributor:
    fullname: Jura
– volume: 316
  start-page: 1039
  year: 2007
  ident: 2022061100531905700_bib36
  article-title: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling
  publication-title: Science
  doi: 10.1126/science.1141478
  contributor:
    fullname: Engelman
– volume: 14
  start-page: 4267
  year: 1995
  ident: 2022061100531905700_bib33
  article-title: Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3
  publication-title: EMBO J
  doi: 10.1002/j.1460-2075.1995.tb00101.x
  contributor:
    fullname: Wallasch
– volume: 111
  start-page: 817
  year: 2014
  ident: 2022061100531905700_bib26
  article-title: Oncogenic KRAS signalling in pancreatic cancer
  publication-title: Br J Cancer
  doi: 10.1038/bjc.2014.215
  contributor:
    fullname: Eser
– volume: 26
  start-page: 921
  year: 2015
  ident: 2022061100531905700_bib20
  article-title: A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial
  publication-title: Ann Oncol
  doi: 10.1093/annonc/mdv027
  contributor:
    fullname: Fuchs
– volume: 4
  start-page: 2516
  year: 2013
  ident: 2022061100531905700_bib49
  article-title: Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels
  publication-title: Nat Commun
  doi: 10.1038/ncomms3516
  contributor:
    fullname: Chauhan
– volume: 91
  start-page: 620
  year: 1999
  ident: 2022061100531905700_bib14
  article-title: Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3
  publication-title: J Natl Cancer Inst
  doi: 10.1093/jnci/91.7.620
  contributor:
    fullname: Ma
– volume: 369
  start-page: 1691
  year: 2013
  ident: 2022061100531905700_bib3
  article-title: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1304369
  contributor:
    fullname: Von Hoff
– volume: 9
  start-page: e106249
  year: 2014
  ident: 2022061100531905700_bib52
  article-title: Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0106249
  contributor:
    fullname: Cao
– volume: 33s
  start-page: suppl; abst 295
  year: 2015
  ident: 2022061100531905700_bib44
  article-title: HER3 as a potential prognostic biomarker in pancreatic cancer
  publication-title: J Clin Oncol
  doi: 10.1200/jco.2015.33.3_suppl.295
  contributor:
    fullname: Wang-Gillam
– volume: 364
  start-page: 1817
  year: 2011
  ident: 2022061100531905700_bib4
  article-title: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa1011923
  contributor:
    fullname: Conroy
– volume: 76
  start-page: 6851
  year: 2016
  ident: 2022061100531905700_bib30
  article-title: Chemoresistance in pancreatic cancer is driven by stroma-derived insulin-like growth factors
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-16-1201
  contributor:
    fullname: Ireland
– volume: 9
  start-page: 754
  year: 2010
  ident: 2022061100531905700_bib27
  article-title: Kinase signaling pathways as targets for intervention in pancreatic cancer
  publication-title: Cancer Biol Ther
  doi: 10.4161/cbt.9.10.11534
  contributor:
    fullname: Preis
– volume: 120
  start-page: 2980
  year: 2014
  ident: 2022061100531905700_bib42
  article-title: Dual blockade of epidermal growth factor receptor and insulin-like growth factor receptor-1 signaling in metastatic pancreatic cancer: phase Ib and randomized phase II trial of gemcitabine, erlotinib, and cixutumumab versus gemcitabine plus erlotinib
  publication-title: Cancer
  doi: 10.1002/cncr.28744
  contributor:
    fullname: Philip
– volume: 387
  start-page: 545
  year: 2016
  ident: 2022061100531905700_bib6
  article-title: Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial
  publication-title: Lancet
  doi: 10.1016/S0140-6736(15)00986-1
  contributor:
    fullname: Wang-Gillam
– volume: 21
  start-page: 418
  year: 2012
  ident: 2022061100531905700_bib51
  article-title: Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2012.01.007
  contributor:
    fullname: Provenzano
– volume: 351
  start-page: 1393
  year: 1998
  ident: 2022061100531905700_bib12
  article-title: Circulating concentrations of insulin-like growth factor-I and risk of breast cancer
  publication-title: Lancet
  doi: 10.1016/S0140-6736(97)10384-1
  contributor:
    fullname: Hankinson
– volume: 436
  start-page: 740
  year: 2013
  ident: 2022061100531905700_bib24
  article-title: IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model
  publication-title: Biochem Biophys Res Commun
  doi: 10.1016/j.bbrc.2013.06.030
  contributor:
    fullname: Jia
– volume: 105
  start-page: 523
  year: 2011
  ident: 2022061100531905700_bib41
  article-title: Targeting ErbB3-mediated stromal-epithelial interactions in pancreatic ductal adenocarcinoma
  publication-title: Br J Cancer
  doi: 10.1038/bjc.2011.263
  contributor:
    fullname: Liles
– volume: 9
  start-page: 665
  year: 2002
  ident: 2022061100531905700_bib13
  article-title: Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells
  publication-title: J Biomed Sci
  doi: 10.1007/BF02254995
  contributor:
    fullname: Liu
– volume: 3
  start-page: 299
  year: 2011
  ident: 2022061100531905700_bib43
  article-title: Rational engineering of antibody therapeutics targeting multiple oncogene pathways
  publication-title: MAbs
  doi: 10.4161/mabs.3.3.15299
  contributor:
    fullname: Fitzgerald
– volume: 13
  start-page: R93
  year: 2011
  ident: 2022061100531905700_bib23
  article-title: erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines
  publication-title: Breast Cancer Res
  doi: 10.1186/bcr3018
  contributor:
    fullname: Knowlden
– volume: 16
  start-page: 321
  year: 2014
  ident: 2022061100531905700_bib47
  article-title: The role of mechanical forces in tumor growth and therapy
  publication-title: Ann Rev Biomed Eng
  doi: 10.1146/annurev-bioeng-071813-105259
  contributor:
    fullname: Jain
– volume: 1766
  start-page: 1
  year: 2006
  ident: 2022061100531905700_bib7
  article-title: IGF-I mediated survival pathways in normal and malignant cells
  publication-title: Biochim Biophys Acta Rev Cancer
  doi: 10.1016/j.bbcan.2006.05.003
  contributor:
    fullname: Kurmasheva
– volume: 279
  start-page: 563
  year: 1998
  ident: 2022061100531905700_bib10
  article-title: Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study
  publication-title: Science
  doi: 10.1126/science.279.5350.563
  contributor:
    fullname: Chan
– volume: 35
  start-page: 973
  year: 2014
  ident: 2022061100531905700_bib11
  article-title: The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma
  publication-title: Tumour Biol
  doi: 10.1007/s13277-013-1131-2
  contributor:
    fullname: Adachi
– volume: 41
  start-page: 143
  year: 2012
  ident: 2022061100531905700_bib2
  article-title: Pancreatic cancer screening
  publication-title: Gastroenterol Clin North Am
  doi: 10.1016/j.gtc.2011.12.001
  contributor:
    fullname: Shin
– year: 2015
  ident: 2022061100531905700_bib1
  article-title: Cancer facts & figures [Internet]
  contributor:
    fullname: American Cancer Society
– volume: 52
  start-page: 4981
  year: 2009
  ident: 2022061100531905700_bib8
  article-title: Inhibition of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase as a novel cancer therapy approach
  publication-title: J Med Chem
  doi: 10.1021/jm9002395
  contributor:
    fullname: Li
– volume: 13
  start-page: 410
  year: 2014
  ident: 2022061100531905700_bib21
  article-title: MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors
  publication-title: Mol Cancer Ther
  doi: 10.1158/1535-7163.MCT-13-0255
  contributor:
    fullname: Fitzgerald
– volume: 9
  start-page: eaal4682
  year: 2017
  ident: 2022061100531905700_bib39
  article-title: The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation
  publication-title: Sci Transl Med
  doi: 10.1126/scitranslmed.aal4682
  contributor:
    fullname: Kodack
– volume: 324
  start-page: 1457
  year: 2009
  ident: 2022061100531905700_bib50
  article-title: Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer
  publication-title: Science
  doi: 10.1126/science.1171362
  contributor:
    fullname: Olive
– volume: 13
  start-page: 392
  year: 2013
  ident: 2022061100531905700_bib17
  article-title: IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer
  publication-title: BMC Cancer
  doi: 10.1186/1471-2407-13-392
  contributor:
    fullname: Hirakawa
– volume: 23
  start-page: 2834
  year: 2012
  ident: 2022061100531905700_bib18
  article-title: A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer
  publication-title: Ann Oncol Off J Eur Soc Med Oncol
  doi: 10.1093/annonc/mds142
  contributor:
    fullname: Kindler
SSID ssj0014104
Score 2.5007942
Snippet Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic...
Purpose: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and...
SourceID proquest
crossref
pubmed
SourceType Aggregation Database
Index Database
StartPage 2873
SubjectTerms 1-Phosphatidylinositol 3-kinase
AKT protein
Apoptosis
Bispecific antibodies
Cancer
Cell survival
Chemotherapy
Design factors
Design standards
ErbB-3 protein
Experimental design
Gemcitabine
Growth factors
Heregulin
In vivo methods and tests
Inhibition
Insulin
Insulin-like growth factor I
Insulin-like growth factor I receptors
Insulin-like growth factors
Paclitaxel
Pancreatic cancer
Phosphorylation
Receptors
Screening
Signaling
Tumor cell lines
Xenografts
Xenotransplantation
Title Dual Inhibition of IGF-1R and ErbB3 Enhances the Activity of Gemcitabine and Nab-Paclitaxel in Preclinical Models of Pancreatic Cancer
URI https://www.ncbi.nlm.nih.gov/pubmed/29549161
https://www.proquest.com/docview/2055385966
https://search.proquest.com/docview/2014956911
Volume 24
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLbKkBAviDuFgYzEW-WSi5O4jyPrLqBN1dikvUWO42h9aDp1iYT4AfwF_i7n2M6lsEnAS1TFp3aU88X-fHwuhHyQqpxh_SoGS3vAeCJjJmEjxJJCxrC6ACeXaO84OY2PLvjny-hyNPo58Fpq6nyqvt8aV_I_WoV7oFeMkv0HzXadwg34DfqFK2gYrn-l4_3GZMq4WubLlvgdHx4w_8wcCcw3-adwMq-uULE3NoZEuWIRIHmoV2pZyxxpJoqfypwtpMKk3d80ZuJA94wucBJrptlEywvozjBNNUmx582Q36atvDJNE5dLqLM5Y4iYKxG_V8hVfyi1cNb8ubG3dLBCIYO0r8YtoPcBSJuNs7Y7x3_nuuwMGL5ARysbwunmXA-T_PJwa1K2gdUt-ILhFCts7ZM_5_5IGDOE622apmcMlmAE4VAeVHi9MoAwR5y-zQX_W9LttukeuY8ZFrEow_7xl-54ivumLmU3lgsNgyf4eOv4mHLa9bjNf-7Y1Bhyc_6YPHK7ErpnIfaEjHT1lDw4cX4Xz8gPRBrtkUbXJbVIowAdapBGW6RRQBptkYaSA6QZ8W2k0WVFB0ijFmn4vx5p1CLtObk4mJ-nR8xV8GAKFoaa8VLwMM5DGZRJPBOBTpT2irJQocrx_Jb7Us5iVSYCaD6whtCT3IMlTyp4V7ARDl-QnWpd6VeEAlfVZeGFWgSSA-0VJY8KLUoV6Bw4ZjEm0_a9Ztc2UUtmNriRyFAnGeokA51kfpKhTsZkt337mfumb7LAi4ABRLM4HpP3XTPMuHiMJiu9blDGWBWAJYzJS6u1bsRWy6_vbHlDHvYfwS7ZqTeNfgu8ts7fGYz9AvJFmaM
link.rule.ids 314,780,784,27924,27925
linkProvider Flying Publisher
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Dual+Inhibition+of+IGF-1R+and+ErbB3+Enhances+the+Activity+of+Gemcitabine+and+Nab-Paclitaxel+in+Preclinical+Models+of+Pancreatic+Cancer&rft.jtitle=Clinical+cancer+research&rft.au=Camblin%2C+Adam+J&rft.au=Pace%2C+Emily+A&rft.au=Adams%2C+Sharlene&rft.au=Curley%2C+Michael+D&rft.date=2018-06-15&rft.issn=1078-0432&rft.volume=24&rft.issue=12&rft.spage=2873&rft_id=info:doi/10.1158%2F1078-0432.CCR-17-2262&rft_id=info%3Apmid%2F29549161&rft.externalDocID=29549161
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1078-0432&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1078-0432&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1078-0432&client=summon